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Indications of spontaneous formation of precursor proteins

12.10.2015

Chemists from the University of Stuttgart observe the formation of complex biomolecules from biochemical basic components

Scientists from the Institute of Organic Chemistry at the University of Stuttgart have determined that under certain conditions spontaneous reactions take place between ribonucleotides and amino acids, leading to molecules that contain ribonucleic acids (RNA) as well as peptides.

The observations indicate a primitive preform of protein synthesis as it could have taken place in the prebiotic evolution. This makes it more probable that life did not start with a pure 'RNA world' but with a molecular world in which RNA as well as the smallest proteins were formed. The results were published in the respected specialist journal Angewandte Chemie (Applied Chemistry).

Life is based on complicated biochemical machinery, the origins of which have not been clear up to now. The most important biochemical machines are enzymes (proteins). The blueprints of the enzymes are deposited in the DNA and are read with the aid of the RNA and enzymes. Without enzymes therefore there is no reading and without blueprints and RNA there are no enzymes.

Up to now the solution for this dilemma was presumed to be that firstly there was a so-called 'RNA world' in which the RNA acted as a blueprint as well as performing tasks similar to enzymes. This hypothesis was supported by experimental findings. Yet how the RNA enzyme world was created from the RNA world was not clear.

Unexpected observation: formation of peptidyl-RNAs

Researchers at the University of Stuttgart have now ascertained that spontaneous reactions take place between the basic components of RNA, the ribonucleotides, and amino acids if they come into contact with each other in a special watery buffer.

The buffer contains a condensation agent that ensures a spontaneous linking of the basic components. Not only RNA chains occur in the mixtures but also mixed forms comprising RNA and peptides (the material on which enzymes and proteins are established). This mixed form is called peptidyl-RNA. Parts of the biochemical machinery for protein synthesis was possibly able to develop from peptidyl-RNAs.

The observation came unexpectedly: the team working for Professor Clemens Richert was actually searching for reaction conditions leading to an enzyme-free reading of RNA sequences. When the doctoral student Mario Jauker established conditions as they could occur in ice-water mixtures when seawater freezes and he added a potent condensation agent, he also observed along with the expected reading process the development of new RNA chains.

Since the condensation agent, an organic derivative of the molecule cyanamide, is also used in peptide synthesis, the chemical engineer Helmut Griesser mixed amino acids to the RNA basic components. Surprisingly not only RNA chains and free peptides occurred in the salty buffer solutions but also peptidyl-RNAs. Such peptidyl-RNAs have long been considered key intermediates of an early form of protein synthesis.

In protein synthesis today (image left) the peptide chain grows up to a protein by it shifting from one transfer-RNA to the next, whereby an amino acid is inserted respectively according to the genetic code. Earlier attempts to induce the formation of peptidyl-RNAs in the absence of enzymes were in vain. The doctrine in this field was that the so-called C-Terminus of the peptide chain and the phosphate group of an RNA component react with each other.

A detailed structural characterisation at the Institute of Organic Chemistry, however, revealed in the case in hand that the contrary, so-called 'N-Terminus' of the peptide chain is linked with the phosphate. This explains why longer peptidyl-RNAs were able to develop. In the case of the structure of the peptidyl-RNAs found now the peptide chain as well as the RNA chain can continue to grow without the involvement of scientists. When adding acetic acids peptides could also then be released from the peptidyl-RNAs.

Yet it is not only peptidyl-RNAs that occur in the water condensation buffer. By adding ancillary materials the researchers were also able to detect compounds that play an important role in the metabolism of the cell. These include adenosine triphosphate (ATP), that is considered to be an energy carrier of the cell, as well as the co-factors NAD and FAD, that occur in the biosynthesis of many cell components as well as the energy supply to the cell.

Puzzle pieces fit better together

It is now clear that under the same reaction conditions it is not only simple genetic material but also preforms of proteins and of key molecules of a primitive metabolism that could occur. Therefore no great evolutionary step is required to get from an 'RNA world' to an 'RNA protein world'. The latter can obviously occur in a similarly spontaneous way like the RNA-chain itself. The fact that this happens under conditions that also lead to the spontaneous copying of genetic information makes these observations all the more fascinating. “Many puzzle pieces now fit together better for us" stated Professor Richert. His team, that now also includes Svenja Kaspari, is currently working on reaction conditions that are even closer to those that are found in the cell today.

Publications in “Angewandten Chemie“ (Applied Chemistry)

The Stuttgart researchers have summarised the results of their studies up to now in two publications that will be published in the respected specialist journal Angewandte Chemie in English as well as in German and that will also be accessible without a subscription: Mario Jauker, Helmut Griesser and Clemens Richert: “Copying RNA sequences without pre-activation", Angewandte Chemie (2015), DOI: 10.1002/ange.201506592 and "Spontaneous formation of RNA strands, peptidyl-RNA and co-factors", Angewandte Chemie (2015), DOI: 10.1002/ange.201506593 Online-Version: http://dx.doi.org/10.1002/ange.201506592 and http://dx.doi.org/10.1002/ange.201506593

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